Molded vial production and its impact on heat transfer while freeze-drying

March 4, 2021March 4, 2021 Vihaan Nagal 0 Comments

Glass vials are the most prevalent primary packaging material utilized in pharmaceutical freeze-drying. It depends on the manufacturing process; tubing or molded vials can be recognized in the market.

The practical significance of each vial type depends on the fill volume of the product: small volume parenterals are typically freeze-dried in tubing vials, while molded vials are fundamentally used for products with larger fill volumes.

The production process of tubing vials is a two-step process with glass tubes as an intermediary outcome. The manufacturing process for molded vials is also routinely made in two steps:

The molten glass is molded into an initial parison with a defined opening and a hollow inside.
This parison is transferred into a second mold where the vial’s ultimate shape is produced by inflating the parison with compressed air.

The formation of the primary parison in the first mold can both be performed by blowing the molten glass with compressed air (“blow-blow,” further abbreviated as BB) or pressing it with a metal plunger (“press-blow,” also abbreviated as PB).

The Press Blow process happens in vials with a more uniform glass weight distribution and wall thickness. However, due to difficulties with the plunger design for narrow-necked containers, it has historically been confined to more wide-necked containers. Recent progress in vial manufacturing has enabled manufacturers to create smaller PB molded vials down to a size of 15-mL injection vials.

The thermal parameters of a container system are of utmost concern to the freeze-drying process. Heat wants to be efficiently conveyed between the heat transfer fluid inside the shelves and the container’s product.

During the freezing stage, heat from the freezing solution must be removed to cool the product to its target freezing temperature adequately. The sublimation process during drying requires energy to be transferred into the product.

The heat transfer coefficient describes the energy transfer rate per area, temperature differential, and time between the freeze-dryer and the container system.

The coefficient for vial freeze-drying is referred to as the vial heat transfer coefficient Kv. Representative Kv values are essential for the quality by design (QbD) approach to develop or transfer freeze-drying cycles: calculating the design space requires Kv as an input parameter.

Knowledge of Kv values for different machines can be used to adapt process parameters during scale-up or transfer of freeze-drying cycles to reduce the number of experiments required for a successful transfer.